Mounting evidence shows that functional connections between the cellular building blocks within the brain actively reorganize, even in the mature brain. Even so, this view is not yet universally accepted in part because tracking these changes in the awake, behaving animal is technically challenging. Further complicating the question of changes in single neuron properties with experience is the fact that cortex comprises many cell types, and recent data from the applicant's laboratory has revealed that plasticity may be expressed differentially across these populations. This proposal focuses on vision as a powerful model system for exploring the role that plasticity plays in normal brain function. The general hypothesis to be tested is that effective visual processing relies on experience driven, adaptive firing patterns of neurons within the inferior temporal cortex (IT), and that this experience leads to differential physiological changes in excitatory and inhibitory neurons. These changes, in turn, support measurable behavioral advantages. Although changes in neural responses are typically slow, artificial control of neural activity can induce modification more rapidly, and this modified activity can guide visually directed behavior. The proposed experiments will support efforts aimed at reviving or augmenting adaptive responses in higher-level visual areas. The proposal has three fundamental aims.
The first aim i s to clearly demonstrate impact of long-term familiarity on visual processing for multiple object classes. The strategy for accomplishing this aim will be to track performance in a speeded recognition tasks with well-known and trial unique stimuli.
The second aim i s to determine how visual experience affects stimulus encoding by neurons in anterior IT cortex. This will be achieved by tracking single neuron and small population activity by combining recording of activity across spatial scales and using carefully generated visual stimuli during the tasks developed in the first aim.
The final aim i s to directly manipulate neuron activity in temporal cortex to control plasticity.
This aim will leverage optogenetic stimulation methods already in use in the applicant's laboratory to affect neural responses on single trials in order to induce the kinds of plasticity observed in the second aim. Together, the results of this work will help bridge the large literature on synaptic plasticity at he cellular level with visual behavior in primates. An important specific focus of these studies will e to identify stimulus, task, and physiological conditions under which both excitatory and inhibitory neurons adapt their responses through long-term experience, and to show how this plasticity can positively influence behavior. That visual experience can profoundly alter visual object representations in IT is of critical importance to efforts directed at repair of the visual system nd in understanding development disorders. Using an innovative set of tools and approaches, the projects in this proposal will emphasize the need to carefully track cellular activity in behaving animals, using complex and demanding real world tasks, with a level of resolution that will likely prove essential for future studies, and models, of higher brain function.

Public Health Relevance

The proposed experiments are relevant to public health as they aim to provide answers about how the visual system develops normally, through experience, to allow for the efficient recognition of complex objects like faces. Understanding this process can guide attempts to restore or augment visual processing in an effective and functionally relevant way. In keeping with the NIH mission to promote creative discovery, to assure capacity to reduce the burden of disease, and to expand medical knowledge that can be shared, the studies and aims seek to test hypotheses about the important relationship between what we see and how we see at the level of brain processes and to develop novel methodologies for controlling this link.

National Institute of Health (NIH)
Research Project (R01)
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Special Emphasis Panel (ZRG1)
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Araj, Houmam H
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Brown University
Schools of Medicine
United States
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Sigurdardottir, Heida M; Michalak, Suzanne M; Sheinberg, David L (2014) Shape beyond recognition: form-derived directionality and its effects on visual attention and motion perception. J Exp Psychol Gen 143:434-54
Woloszyn, Luke; Sheinberg, David L (2012) Effects of long-term visual experience on responses of distinct classes of single units in inferior temporal cortex. Neuron 74:193-205
Monosov, Ilya E; Sheinberg, David L; Thompson, Kirk G (2011) The effects of prefrontal cortex inactivation on object responses of single neurons in the inferotemporal cortex during visual search. J Neurosci 31:15956-61
Singer, Jedediah M; Sheinberg, David L (2010) Temporal cortex neurons encode articulated actions as slow sequences of integrated poses. J Neurosci 30:3133-45
Woloszyn, Luke; Sheinberg, David L (2009) Neural dynamics in inferior temporal cortex during a visual working memory task. J Neurosci 29:5494-507
Kawasaki, Keisuke; Sheinberg, David L (2008) Learning to recognize visual objects with microstimulation in inferior temporal cortex. J Neurophysiol 100:197-211
Anderson, Britt; Mruczek, Ryan E B; Kawasaki, Keisuke et al. (2008) Effects of familiarity on neural activity in monkey inferior temporal lobe. Cereb Cortex 18:2540-52
Anderson, Britt; Sheinberg, David L (2008) Effects of temporal context and temporal expectancy on neural activity in inferior temporal cortex. Neuropsychologia 46:947-57
Singer, Jedediah M; Sheinberg, David L (2008) A method for the real-time rendering of formless dot field structure-from-motion stimuli. J Vis 8:8.1-8
Anderson, Britt; Sanderson, Mark I; Sheinberg, David L (2007) Joint decoding of visual stimuli by IT neurons'spike counts is not improved by simultaneous recording. Exp Brain Res 176:1-11

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